Panayiotis Anastasis

Cyclisation of farnesyl pyrophosphate to γ-bisabolene in tissue cultures of Andrographis paniculata

Tissue Cultures of Andrographis paniculate transform trans,trans-[1-3H2; 12,13-14C2]farnesy pyrophosphate, and (3R,5R)- and (3R,5S)-(5-3H)-mevalonolactones into Z-γ-bisabolene without tritium loss; the absolute configuration of paniculide B (7a) has been determined by an X-ray crystal structure determination of its bis-p-bropmobenzoate.

On the role of leucine in terpenoid metabolism

Incorporation of [2-13C]-, [3-13C]-, (4R)-[5-13C]- and (4S)-[5-13C]-leucines into paniculide by tissue cultures of Andrographis paniculata shows that (a)(3S)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) from leucine breakdown is not incorporated direct into mevalonic acid (MVA) but that (b) both the acetyl-CoA and acetoacetate produced by leucine breakdown via HMG-CoA are subsequently incorporated into HMG-CoA and MVA.

The role of leucine in isoprenoid metabolism. Incorporation of [3-13C]leucine and of [2-3H,4-14C]-β,β-dimethylacrylic acid into phytosterols by tissue cultures of Andrographis paniculata

[3-13C]Leucine is incorporated into phytosterols by tissue cultures of Andrographis paniculata by breakdown to acetyl-CoA and its subsequent incorporation via(3S)-3-hydroxy-3-methylglutaryl-CoA(HMG-CoA) and mevalonic acid; [2-3H,4-14C]-β,β-dimethylacrylic acid also is not incorporated intact.

Studies of chromenes. Part 4. Oxidation of hexahydro-5H-chromeno[3,4-c]-pyridazines and conformational isomerism in tetra-and hexa-hydro-N,N′-dialkoxycarbonyl-5H-chromeno[3,4-c]pyridazines

3,4-Bis(t-butoxycarbonyl)- and 3,4-bis(methoxycarbpnyl)-8-methoxy-5,5-dimethyl-2,3,4,4a-tetra-hydro-5H-chromeno[3,4-c]pyridazines and their 2,2-dimethyl analogues were hydrogenated to give hexahydrochromenopyridazines possessing only a trans-ring junction. Removal of the t-butoxy-carbonyl groups from the trans-products afforded the corresponding 1,2,3,4,4a,10b-hexahydro-5H-chromeno[3,4-c]pyridazines which were oxidised first to 1,2,3,10b-tetrahydro- and then 1,2-dihydro-5H-chromenopyridazines. The last-named dihydro compounds possess an unusual [3,4]pyridazine hydrogenation pattern. The dialkoxycarbonyl derivatives of both the tetra- and hexahydrochromenopyridazines exist as pairs of conformational isomers whose interconversion is acid catalysed. The isomerism is considered to be due to restricted rotation about the less hindered N(3)–CO bond, the N(4)–CO bond being locked in one conformation by 1,3 interactions.

The role of leucine in terpenoid metabolism. Incorporation of [2-13C]- and [3-13C]-leucines into sesquiterpenoids by tissue cultures of Andrographis paniculata

Incorporation of [3-13C]-leucines into paniculides by tissue cultures of Andrographis paniculata shows that (a)(3S)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) from leucine breakdown is not incorporated intact into paniculide and (b) leucine is incorporated by breakdown to acetyl-CoA and its subsequent incorporation via HMG-CoA and MVA.

Analogues of antijuvenile hormones

Several analogues of precocenes I and II have been synthesized, including derivatives of 6,7-dihydroxy-2,2-dimethylchromen, 7,8-dihydroxy-2,2-dimethylchromen, 7-hydroxy-2,2-dimethyl-6-nitrochromen, and 6-amino-7-hydroxy-2,2-dimethylchromen. 5,6-Dimethoxy-3,3-dimethylindene was also synthesized. Improved procedures for the dehydration of chroman-4-ols to chromens and for the reduction of chroman-4-ones to chroman-4-ols are reported. Analogues have been tested for activity in the brown planthopper Nilaparvatus lugens Stal. None had significant morphogenetic effects, but two possessed insecticidal activity and showed both antagonism and synergism when used in conjunction with permethrin.

Studies of chromenes. Part 5. Reaction of the Vilsmeier reagent with 7-methoxy-2,2-dimethylchroman-4-ones. 4-Chloro-7-methoxy-2,2-dimethyl-2H-chromenes and their nitration products.

Action of the Vilsmeier reagent on 7-methoxy-2,2-dimethylchroman-4-one and its 6-bromo and 6-methoxy analogues gave low yields of 4-chlorochromene-3-carbaldehydes. 4-Chloro-2H-chromenes, which are not precursors of the carbaldehydes, were obtained in high yields. 4-Chloro-7-methoxy-2,2-dimethyl-6-nitrochroman was too labile to allow a dehydrogenation to the 6-nitrochlorochromene but the latter was obtained by regioselective nitration of 4-chloro-7-methoxy-2,2-dimethyl-2H-chromene. 6-Amino-7-methoxy-2,2-dimethylchroman-4-one, protected as the N-ethoxycarbonyl derivative, gave the 6-aminochlorochromene. The 6-amino-5-chloro analogue largely underwent N-formylation. The chlorochromenes have potential synthetic value since those without electron-withdrawing substituents are readily hydrolysed back to the chroman-4-one.

Studies of chromens. Part 2. Synthesis of 7-methoxy-2,2-dimethylchromen-3-carboxylic acid

The preparation of the title compound (1a) is described. Effects of C-2 methyl groups on ring opening and alkylation of chroman-4-ones under basic conditions are discussed. The reaction of hydrazine with 3-ethoxycarbonyl-7-methoxy-2,2-dimethylchromen (1d) and 3-ethoxycarbonyl-7-methoxy-2,2-dimethylchroman-4-one (3f) failed to give the pyrazolidinone or pyrazolinone.

Studies of chromens. Part 3. Routes to 2,2-dimethylchroman-3-ones and 4-ethyoxycarbonyl-2,2-dimethylchromens. Synthesis of a stable chromenopyrazolinone

2,2-Dimethyl-3,4-epoxychroman (6a) was converted into 2,2-dimethylchroman-3-one which readily underwent ethoxycarbonylation to 4-ethoxycarbonyl-2,2-dimethylchroman-3-one (5c). The derived 4-ethoxycarbonyl-2,2-dimethylchromen (1b) reacted with hydrazine to give the pyrazolidinone (4a), oxidation of which gave the stable pyrazolinone (11). Lead tetra-acetate acetoxylation of 7-methoxy-2,2-dimethylchroman-4-one, followed by metal hydride reduction, afforded the 3,4-diol as a mixture of isomers. The relative proportions of cis and trans isomers could be varied from 1:1 to 5:1, respectively, by the choice of reducing conditions. Acid-catalysed dehydration of the diol mixture gave 7-methoxy-2,2-dimethylchroman-3-one (5b). This was unstable and could not be ethoxycarbonylated, but 4-ethoxycarbonyl-7-methoxy-2,2-dimethylchroman-3-one (5d)/(1j) was obtained by a standard synthesis.

Transannular cyclisation products of a 7-ethyl idenebicyclo[3.3.2]decan-3-one

Reaction of the enone 1 with toluene-p-sulphonic acid in solvent toluene at reflux furnished the products of ring closure 7–11.